Eye genes: Looking forward, glancing back

Abstract

AbstractWhen we began the identification of genes implicated in eye disease, the process was slow and laborious. It is three decades since we identified PAX6 as the gene mutated in aniridia, before the launch of the Human Genome Project. Since then there have been seismic changes in technology: in sequencing, gene expression studies, including database generation and data mining and the use of AI (artificial intelligence). The building of the Human Cell Atlas is revolutionizing our understanding of microanatomy. Patient phenotyping has also evolved with great strides in ocular imaging and psychophysics. Two decades ago, we identified further key eye development genes, SOX2 and OTX2, implicated in anophthalmia and microphthalmia. Together with retinal disease gene discovery, the era of functional network building began. Our interests encompassed defining not only coding region mutations—now much aided by advances in protein structure prediction—but also non‐coding regulatory variation. Exploration of dynamic and established genome organization is contributing to improved understanding of these aspects normal and abnormal function. Our speedy tour will take us through much territory.